Evolutionary biologist Richard Lenski at Michigan State University spends a lot of time thinking about how microbes grow. Since 1988, his team has watched populations of Escherichia coli bacteria grow and evolve in the lab through more than 73,000 generations. So when cases of COVID-19, caused by the novel coronavirus SARS-CoV-2, appeared in the United States, he knew to expect exponential growth-these first cases were just a hint of what was to come.
This week, as research institutions around the world brace for a surge in COVID-19 cases and consider their staff and students' roles in slowing the virus' spread, Lenski decided to freeze his bacteria and pause the 32-year experiment. "I didn't want people responsible for doing this daily work [of maintaining the bacteria] to feel a pressure to come in when they might not be feeling well," he says. This is "a tiny perturbation" in the scheme of the experiment, which can simply be resumed by unfreezing the bacteria. But that disruption is itself the tip of an iceberg. Countless labs in a variety of research fields are reconsidering their planned studies-and not all projects can be easily put on ice.
Measures to control the spread of the virus vary by university and often reflect the local severity of the outbreak. Many researchers told Science Insider that none of the disruptions to their work compare to the human toll of the pandemic. Some institutions are allowing researchers lab access while aiming to minimize the number of people gathering in buildings. Others are discouraging all in-lab research. Harvard University's college of arts and sciences shifted from the former category to the latter yesterday. Its dean called for a "ramp-down of research activities" by 18 March, followed by a 6- to 8-week period of "suspended lab access."
For many researchers there, a key concern is maintaining colonies of research mice should the university's animal care team be short-staffed during the outbreak. Evolutionary biologist Hopi Hoekstra suspects she'll have to reduce her group's mouse colonies at least by half-by hundreds of animals-which may require killing mice. Many of her team's mouse strains were collected from the wild and are studied because of their unique behaviors. Supplies of many types of lab mice can later be replenished from a large vendor, she says, but, "If something happens, or they're not getting long-term care and we reduce the colony so much that we can't keep them going, [those unique mice are] lost forever."
Academic medical centers are considering how to keep thousands of clinical trials up and running while minimizing risk to patients and staff. "We are evaluating clinical trials one by one," says Jonathan Epstein, executive vice dean and chief scientific officer at the University of Pennsylvania (UPenn). "That means discontinuing all contact that might contribute to [the] spread" of the virus.
At Johns Hopkins University, Baltimore, the school divvied its clinical research protocols-a subset of which test drugs-into three tiers. The first qualified as essential either because the trials cover potential COVID-19 treatments, such as one in which researchers are testing the Gilead antiviral remdesivir, or because they address certain acute, life-threatening conditions, such as a trial of a therapy for the neurological disorder Huntington disease. These studies-representing about 10% to 15% of Hopkins's 1500 clinical studies-can continue normally, including enrolling new patients.
Trials that fall into the second tier have halted new enrollment, but they can continue as long as they limit face-to-face contact. In these cases, which include many cancer trials, investigators are trying to send study drugs by mail where possible and minimize time spent in waiting rooms.
The third tier includes cohort studies that follow volunteers long-term, including the Multi-Ethnic Study of Atherosclerosis (MESA). "We have said that they can continue only through what you can do through online or by telephone," says Dan Ford, the university's vice-dean for clinical investigation.
Ford, who is part of the team that stratified these trials, is trying to weigh the risks and benefits of slowing or halting trials for at least 2 months. Investigators, he says, "can see that as not being a giant problem," including an obesity researcher testing a new surgical procedure. "He said, 'I have five people lined up [to join the study] but I should stop,'" a view with which Ford agreed. However, if the delay stretches longer-to 1 year, for example-"there will be another reassessment."
UPenn is acting along similar lines, trying to continue the trials it can, especially for patients most in need, while blunting risk of viral transmission. "We are trying to avoid having any patient come to the hospital purely for research purposes," Epstein says. This means removing checkups from clinical protocols where possible and shipping drugs to patients. In some cases, the changes mean deviating from a trial's planned protocol. "We're hopeful that regulatory agencies would understand" this decision, even if it affects the kind of data investigators can gather, Epstein says.
Exceptions include analogs to John Hopkins's first tier: Many cancer patients at the university are enrolled in trials as a last-ditch hope, and for them, treatments will continue-with new volunteers potentially enrolling, too.
Researchers whose work depends on international travel are already abandoning plans. Epidemiologist Camila González-Beiras of the Fight AIDS and Infectious Diseases Foundation flew to Papua New Guinea in late February expecting to wrap up a roughly 50,000-person trial comparing two strategies for administering the antibiotic azithromycin for the ulcer-causing skin disease yaws. The team already had preliminary evidence that three doses offered longer-lasting protection than the currently recommended single dose, and was returning mainly for ethical reasons: to give an extra dose to those who had been in the study's one-dose comparison group and to look for potentially drug-resistant cases.
But last week, Papua New Guinea's health department suggested that González-Beiras and her team call off the trip. Funding for the project from the health department and the World Health Organization was uncertain, and national health officials collaborating on the project had been rerouted to the airport to help with COVID-19 screening. Although González-Beiras was already in Papua New Guinea, having flown from a vacation in the Philippines, five other team members would be coming from Spain, which now has more than 4000 COVID-19 cases. Their travel to Papua New Guinea, which has no documented cases yet, "would be very irresponsible," she says.
She's now trying to book flights home and is optimistic that the communities where her team has worked are now equipped to spot and manage new yaws cases, even if the project didn't end as planned. Those who didn't get the extra doses should still be protected for 2 years or more. "I think it should be fine," she says. "I hope it will be fine."
The research vessel Polarstern, frozen in ice and drifting around the North Pole on the yearlong MOSAiC mission to study the effects of climate change on the Arctic, would be a very bad place for COVID-19 to take hold. The ship had a near miss this week, when a member of the crew slated to fly on the research airplane that collects atmospheric data for the expedition tested positive for SARS-CoV-2. That team member had attended a preparation session in Bremerhaven, Germany, on 5 March. Everyone at the session was tested as a precaution. More than 20 participants are now in quarantine at home for at least 2 weeks.
The research flight team was slated to depart on 11 March, so the quarantine means the flights will be delayed, says MOSAiC expedition leader Markus Rex, an atmospheric scientist at the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research. (Update, March 16: The flights had to be canceled due to travel restrictions.) Although the infected team member wasn't slated to join the ship itself, Rex says, he could have infected staff at the Svalbard, Norway, staging site. Future crew members, both the aircraft team and the team slated to travel to the ship in April, will be tested twice, once before leaving home and again at the staging site, Rex says. The ship does have the ability to isolate an ill person, he says, but a COVID-19 infection "is something we want to avoid with all means possible."
Travel restrictions have twice vexed Michael Clark, an astrophysicist and postdoc at Purdue University. He works on XENON, a detector in Italy's subterranean Gran Sasso National Laboratory that's searching for hypothetical particles of dark matter. Clark arrived there in February to help install the latest, biggest version of the detector. He intended to go back to Purdue briefly and return in early March, but when his university announced restrictions on travel to Italy, he stayed to avoid getting stuck in the United States.
Then on 11 March, President Donald Trump announced a ban on non-Americans flying from Europe, and Clark, a Canadian, thought he had to get home while the going was good. He plonked down $2220 for a Friday flight to Chicago. The lab appeared to be preparing to close anyway, Clark says. The 160-member XENON team had installed the new detector's delicate innards and were racing to close up its outer container. "There's sort of a rush right now to make sure we get the detector into a safe situation," he says. He faces 14 days of self-quarantine, which he says he'll use to analyze data from the previous version of XENON.
In Lombardy, the region of Italy most affected by the coronavirus, structural biologist Federico Forneris fears months of lockdown could permanently change the direction of his research. His University of Pavia lab studies synapse formation as well as collagen production and its possible implications in cancer metastasis. Since Monday, his university has allowed only faculty and technicians-not Ph.D. students or postdocs-to enter labs, and only for essential tasks such as keeping cell lines or lab animals alive. Forneris doesn't have a technician, so he's urging his university to let in a student or postdoc to tend to cultured cells.
"Most of the lab work is stopped," he says. Members of his lab are working from home, reading papers and analyzing data. If the lockdown goes on for too long, he might have to shift the focus of his research to computational biology, which can be done as telework.
The spread of the virus has slowed work at the world's biggest atom smasher, the Large Hadron Collider (LHC) near Geneva, Switzerland. The 27-kilometer-long accelerator has been down since December 2018 for 2 years of upgrades to it and the four gigantic particle detectors it feeds. Physicists actually need more access to the machinery now than when it's running, says John Hobbs, a particle physicist at Stony Brook University. CERN, the European particle laboratory and home to the LHC, has restricted access to essential personnel.
The efficiency of the work has suffered. Hobbs and about 5000 other far-flung researchers working with the enormous ATLAS particle detector are struggling to coordinate remotely with much smaller teams on site. "I've spent probably 3 hours over the past 24 on Skype with somebody, guiding him through the installation of one bit of our electronics," Hobbs says. Normally, installation would take about an hour. "He says something then points the webcam at what we're looking at, then we talk a little bit more."
He says without knowing how long access to CERN will be restricted, he can't say whether the entire LHC upgrade will be delayed.
Cancer geneticist Alberto Bardelli had just 48 hours to close his lab at the University of Turin in Italy, after receiving a 7 March email from the institute's scientific director and director general. When he told the 25 members of his lab about the closure, some cried. "The lab becomes a second family," he says.
The researchers scrambled to freeze patient samples, but they don't know if these will be usable once thawed. One person is allowed to enter the lab each day to check that essential equipment is working, but tissue collection and analysis to support clinical trials has halted.
Bardelli now worries he won't be able to fulfill the commitments in several national and European grants his lab has received. "I hope that we will be given the opportunity to extend the deadlines for reports and deliverables," he says. He also laments projects started at his institute that have been stalled-including an effort to develop a diagnostic test for the new coronavirus.
Angst over missed opportunities is widespread. With Lenski's E. coli experiment safely frozen, he is sharing his ramp down plan with other research groups and joining a chorus of scientists urging colleagues to resist the urge to get lab work done at the expense of spreading the virus in their communities. "It's going to be disruptive to science," he says, "but it also reminds us that we have ordinary lives and connections to people that we need to safeguard."
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